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dc.contributor.authorSchafer, Dorothy P
dc.contributor.authorHeller, Christopher T.
dc.contributor.authorGunner, Georgia
dc.contributor.authorHeller, Molly
dc.contributor.authorGordon, Christopher
dc.contributor.authorHammond, Timothy
dc.contributor.authorWolf, Yochai
dc.contributor.authorJung, Steffen
dc.contributor.authorStevens, Beth
dc.date2022-08-11T08:09:45.000
dc.date.accessioned2022-08-23T16:41:52Z
dc.date.available2022-08-23T16:41:52Z
dc.date.issued2016-07-26
dc.date.submitted2016-08-10
dc.identifier.citation<p>Elife. 2016 Jul 26;5. pii: e15224. doi: 10.7554/eLife.15224. <a href="http://dx.doi.org/10.7554/eLife.15224">Link to article on publisher's site</a></p>
dc.identifier.issn2050-084X (Linking)
dc.identifier.doi10.7554/eLife.15224
dc.identifier.pmid27458802
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39973
dc.description.abstractMicroglia, the resident CNS macrophages, have been implicated in the pathogenesis of Rett Syndrome (RTT), an X-linked neurodevelopmental disorder. However, the mechanism by which microglia contribute to the disorder is unclear and recent data suggest that microglia do not play a causative role. Here, we use the retinogeniculate system to determine if and how microglia contribute to pathogenesis in a RTT mouse model, the Mecp2 null mouse (Mecp2(tm1.1Bird/y)). We demonstrate that microglia contribute to pathogenesis by excessively engulfing, thereby eliminating, presynaptic inputs at end stages of disease ( > /=P56 Mecp2 null mice) concomitant with synapse loss. Furthermore, loss or gain of Mecp2 expression specifically in microglia (Cx3cr1(CreER);Mecp2(fl/y)or Cx3cr1(Cr)(eER); Mecp2(LSL/y)) had little effect on excessive engulfment, synapse loss, or phenotypic abnormalities. Taken together, our data suggest that microglia contribute to end stages of disease by dismantling neural circuits rendered vulnerable by loss of Mecp2 in other CNS cell types.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=27458802&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © 2016, Schafer et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectMecp2
dc.subjectRett Syndrome
dc.subjectengulfment
dc.subjectmicroglia
dc.subjectmouse
dc.subjectneuroscience
dc.subjectsynapse
dc.subjectMolecular and Cellular Neuroscience
dc.titleMicroglia contribute to circuit defects in Mecp2 null mice independent of microglia-specific loss of Mecp2 expression
dc.typeJournal Article
dc.source.journaltitleeLife
dc.source.volume5
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3787&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2782
dc.identifier.contextkey8956655
refterms.dateFOA2022-08-23T16:41:52Z
html.description.abstract<p>Microglia, the resident CNS macrophages, have been implicated in the pathogenesis of Rett Syndrome (RTT), an X-linked neurodevelopmental disorder. However, the mechanism by which microglia contribute to the disorder is unclear and recent data suggest that microglia do not play a causative role. Here, we use the retinogeniculate system to determine if and how microglia contribute to pathogenesis in a RTT mouse model, the Mecp2 null mouse (Mecp2(tm1.1Bird/y)). We demonstrate that microglia contribute to pathogenesis by excessively engulfing, thereby eliminating, presynaptic inputs at end stages of disease ( > /=P56 Mecp2 null mice) concomitant with synapse loss. Furthermore, loss or gain of Mecp2 expression specifically in microglia (Cx3cr1(CreER);Mecp2(fl/y)or Cx3cr1(Cr)(eER); Mecp2(LSL/y)) had little effect on excessive engulfment, synapse loss, or phenotypic abnormalities. Taken together, our data suggest that microglia contribute to end stages of disease by dismantling neural circuits rendered vulnerable by loss of Mecp2 in other CNS cell types.</p>
dc.identifier.submissionpathoapubs/2782
dc.contributor.departmentSchafer Lab
dc.contributor.departmentNeurobiology
dc.source.pagese15224
dc.contributor.studentGeorgia Gunner
dc.description.thesisprogramNeuroscience


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Copyright © 2016, Schafer et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Except where otherwise noted, this item's license is described as Copyright © 2016, Schafer et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.